Spatial isotope deep tracing deciphers inter-tissue metabolic crosstalk

作者：Xinzhu Li, Ying Zhu, Ting Li, Xinyi Tu, Shiyu Zhu, Lingzhi Wang, Fang Li, Chenglong Sun, Xin Li, Haiyi Zhao, Tang Tang, Qingce Zang, Ruiping Zhang, Zeper Abliz · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-63243-2 · 被引用次数：12 · 研究领域：Metabolomics and Mass Spectrometry Studies、Molecular Biology Techniques and Applications、Advanced MRI Techniques and Applications

Organs collaborate to maintain metabolic homeostasis in mammals. Spatial metabolomics makes strides in profiling the metabolic landscape, yet can not directly inspect the metabolic crosstalk between tissues. Here, we introduce an approach to comprehensively trace the metabolic fate of 13C-nutrients within the body and present a robust computational tool, MSITracer, to deep-probe metabolic activity in a spatial manner. By discerning spatial distribution differences between isotopically labeled metabolites from ambient mass spectrometry imaging-based isotope tracing data, this approach empowers us to characterize fatty acid metabolic crosstalk between the liver and heart, as well as glutamine metabolic exchange across the kidney, liver, and brain. Moreover, we disclose that tumor burden significantly influences the host’s hexosamine biosynthesis pathway, and that the glucose-derived glutamine released from the lung as a potential source for tumor glutamate synthesis. The developed approach facilitates the systematic characterization of metabolic activity in situ and the interpretation of tissue metabolic communications in living organisms. Organ metabolic crosstalk is vital but challenging to trace. Here, the authors present MSITracer, a computational tool for spatial isotope tracing that reveals inter-organ crosstalk, such as liver–heart fatty acid metabolism and lung-derived glutamine catabolism in tumors.